LolCDE lipoprotein transport complex (LolCDE)

The LolCDE lipoprotein transport complex is an essential ATP-binding cassette (ABC) transporter located in the inner membrane of Gram-negative bacteria (UniProt: P0AE05, P0AE08, P0AE11). It is composed of the membrane proteins LolC and LolE, along with the ATPase LolD, which provide the energy required to extract lipoproteins from the inner membrane and transfer them to the periplasmic chaperone LolA (PubMed: 11134031). This transport mechanism is fundamental for the biogenesis of the bacterial outer membrane, a structure critical for survival and antibiotic resistance (PubMed: 30104374). Because the Lol pathway is essential and highly conserved across many Gram-negative pathogens, it has emerged as a high-priority target for novel antimicrobial development. Recent research has identified selective inhibitors such as lolamicin, which can target the LolCDE complex in pathogenic bacteria while minimizing impact on the gut microbiome (Nature: 10.1038/s41586-024-07502-0). Inhibition of LolCDE leads to the toxic accumulation of lipoproteins in the inner membrane, ultimately resulting in bacterial cell lysis.

Other names

Localization of lipoprotein systemLolCDE ABC transporterLipoprotein-releasing ABC transporterLolCDE complex

Inhibition of the ATP-dependent release of lipoproteins from the inner membrane to the periplasmic chaperone LolA, thereby disrupting outer membrane assembly (PubMed: 25114291).